Because the incidence of age-related diseases generally doubles with every 10 years of life, the identification of genes associated with risk of a disease can provide a route to early diagnosis and possible points of intervention. We have shown see ZO1 on Gene-finding and longitudinal studies for aging-associated conditions in a Sardinian population cohort (SardiNIA2) that studies of the population of Sardinia can infer strong signals for genes associated with a wide variety of traits, including risk factors for cardiovascular disease. This Project is designed to capitalize on the findings in two ways. In one approach, the genes associated with specific risk factor traits, including those identified as involved in the levels of the pulse wave velocity of blood and in the levels of serum uric acid, are being studied to investigate the precise variation in the gene that causes the difference in physiology, and the biochemical basis for the effects of those genes on those traits. In a second approach, the genetic studies are being extended to clinical series of Sardinian patients and controls for several diseases, including autoimmune and cardiovascular diseases. The notion that the inter-relatedness in the Sardinian population can simplify the genetic analyses is supported by a first successful study has revealed a gene that makes a link between inflammation in the lung and asthma (IRAK-M).